Neurophysins, the intraneuronal peptides which are synthesized with the hormones of the posterior pituitary, oxytocin and vasopressin, have proven to be a major secretory product of the neurohypophysis. This new measure of posterior pituitary function has been applied to the study of human physiology and pathology. We have developed specific radioimmunoassays for two neurophysins in the human, and demonstrated independent secretion of each. Studies during this grant award have proven that one neurophysin is a vasopressin-neurophysin and the second is an oxytocin-neurophysin. Secretion of vasopressin and vasopressin-neurophysin are being investigated during diseases which are associated with abnormal water balance including: diabetes insipidus, the syndrome of inappropriate ADH secretion, Addison's Disease, myxedema, neurosurgical hyponatremia, etc. We have proven that estrogen is a stimulus for the secretion of oxytocin-neurophysin. This raises the possibility that oxytocin plays a role in reproduction independent of its role at parturition. That is, oxytocin may be involved in the regulation of gondotropin secretion and/or the effects of gonadotropin on the ovary and uterus. Other studies in the rat have outlined the development of the neurohypophyseal system in the developing fetus and the secretion of vasopressin and oxytocin in infant rats as model of abnormal water balance in infant humans. This is a comprehensive study of the anatomy, pathology, physiology and pathophysiology of all of the known peptides which are secreted by the neurohypophysis.